For several years, we have been studying in molecular detail the primary genetic response of human peripheral blood T cells to mitogenic activation. By employing subtractive cloning technology, we have previously isolated in excess of 60 genes whose expression is induced within hours of cellular stimulation. Included among these genes are well-known lymphokines, receptors and oncogenes in addition to many novel genes whose functions we are investigating. To date we have discovered a number of genes important for proliferation and the expression of a differentiated T cell phenotype; these include two novel lymphokines, three zinc finger proteins, factors which bind DNA, a steroid receptor protein, a novel phosphatase, a ras oncogene-related protein, a transmembrane receptor closely related to a receptor involved in signalling during cell killing by natural killer cells and two genes which belong to a new family of NF-KasppaB transcription factors. We have pursued both functional as well as regulatory aspects of several selected novel genes. One of the zinc finger genes, 225, is deregulated in its expression by transformation with the human T leukemia virus, suggesting a potential function of this protein in cellular transformation. Drosophila genes sharing a similar zinc finger domain have been cloned to understand function in a genetically more easily manageable system. NF-KappaB complexes regulate expression of many inducible genes including most lymphokines/cytokines as well as many viruses like human immunodeficiency virus and cytomegalovirus. We have demonstrated that these many pleiotropic effects are likely to be mediated by several distinct factors including one made up of relB and rik two novel mitogen inducible rel-related proteins distinct from any previously described constituents of NF-KappaB. These two factors heterodimerize and bind to KappaB sites and transactivate such sites in cells in vivo.